There is considerable uncertainty concerning the nature of cells responsible for the degradation of bone and other connective tissues. The current study is an investigation of the mechanisms of enzymatic resorption of collagen and bone matrix through an evaluation of the interrelationships of osteoclasts, macrophages and foreign body giant cells. Our specific objective is to determine why osteoclasts and giant cells (both derived from macrophages) exhibit distinct lysosomal enzyme profiles and ultrastructure. Two hypotheses will be tested: (1) that osteoclasts derive, in part, from cells other than the macrophage and are therefore under different genetic control, or (2) that all giant cells are essentially the same and that osteoclast characteristics are induced by contact with, or resorption of, bone. Experiments will also be conducted to determine whether functionally-defective osteoclasts (from osteopetrotic rodents) are derived from defective macrophages or only develop their deficiency after formation from normal macrophage fusion. These questions will be studied in normal and osteopetrotic animals by applying lysosomal enzyme histochemistry, biochemistry, and electron microscopy techniques to routine cell cultures and potassium permanganate-induced calcergy models.